4-tert-butyl-N-[3-[(2-oxo-6-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaenyl)amino]phenyl]benzamide | 1395923-00-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 4-tert-butyl-N-[3-[(2-oxo-6-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaenyl)amino]phenyl]benzamide
• CAS: 1395923-00-8
• 化学式: C₃₂H₃₀N₂O₂
• 分子量: 474.602
• InChiKey: NJQNBKORQYQAJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  间氯氯苄 在 aluminum (III) chloride 、 草酰氯 、 10% Pd/C 、 氢气 、 palladium diacetate 、 N,N-二甲基甲酰胺 、 三苯基膦 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 15.75h， 生成 4-tert-butyl-N-[3-[(2-oxo-6-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaenyl)amino]phenyl]benzamide
  参考文献：
  名称：

  Targeting the Hinge Glycine Flip and the Activation Loop: Novel Approach to Potent p38α Inhibitors

  摘要：

  The p38 MAP kinase is a key player in signaling pathways regulating the biosynthesis of inflammatory cytokines. Small molecule p38 inhibitors suppress the production of these cytokines. Therefore p38 is a promising drug target for novel anti-inflammatory drugs. In this study, we report novel dibenzepinones, dibenzoxepines, and benzosuberones as p38 alpha MAP kinase inhibitors. Previously reported dibenzepinones and dibenzoxepines were chemically modified by introduction of functional groups or removal of a phenyl ring. This should result in targeting of the hydrophobic region I, the "deep pocket", and the hinge glycine flip of the kinase. Potent inhibitors with IC50 values in the single digit nanomolar range (up to 3 nM) were identified. Instead of targeting the "deep pocket" in the DFG-out conformation, interactions with the DFG-motif in the in-conformation could be observed by protein X-ray crystallography.

  DOI：

  10.1021/jm300951u

文献信息

• Targeting the Hinge Glycine Flip and the Activation Loop: Novel Approach to Potent p38α Inhibitors
  作者：Kathrin E. Martz、Angelika Dorn、Benjamin Baur、Verena Schattel、Márcia I. Goettert、Svenja C. Mayer-Wrangowski、Daniel Rauh、Stefan A. Laufer

  DOI：10.1021/jm300951u

  日期：2012.9.13

  The p38 MAP kinase is a key player in signaling pathways regulating the biosynthesis of inflammatory cytokines. Small molecule p38 inhibitors suppress the production of these cytokines. Therefore p38 is a promising drug target for novel anti-inflammatory drugs. In this study, we report novel dibenzepinones, dibenzoxepines, and benzosuberones as p38 alpha MAP kinase inhibitors. Previously reported dibenzepinones and dibenzoxepines were chemically modified by introduction of functional groups or removal of a phenyl ring. This should result in targeting of the hydrophobic region I, the "deep pocket", and the hinge glycine flip of the kinase. Potent inhibitors with IC50 values in the single digit nanomolar range (up to 3 nM) were identified. Instead of targeting the "deep pocket" in the DFG-out conformation, interactions with the DFG-motif in the in-conformation could be observed by protein X-ray crystallography.